Although outer hair cells (OHC) play a major role in amplifying mechanical energy in the inner ear, it is the inner hair cells (IHC), which contact 90-95% of the auditory afferent fibers that relay information to the brain. To date, the effects of selective IHC loss on auditory perception are not well understood despite their importance coding both simple and complex signals such as speech. The overall goal of this project is to characterize and quantify the effects of selective IHC loss on hearing sensitivity, hearing in noise, and temporal processing. Importantly, in the chinchilla, carboplatin, an anticancer drug, selective damages IHC and type-I auditory nerve fibers. The purpose of this proposal is to use the chinchilla model to identify specific auditory deficits that occur as a function of IHC loss. Clinical tests, for cochlear dead regions, are currently in use to determine areas of the cochlea where IHC presumably no longer exist. However, the relationship between the extent of partial IHC loss and functional hearing deficits is largely unknown. Clinically, it has been suggested that IHC pathology could play a role in Auditory Neuropathy (AN) or Auditory Dyssynchrony (AD) 1. To determine what functional deficits are associated with IHC loss, chinchillas will be trained to perform five auditory tasks that measure different aspects of auditory perception: (1a) Pure-tone thresholds in quiet to determine hearing sensitivity, (1b) pure-tone thresholds in the presence of broadband noise to assess signal in noise peformance and (1c) tone thresholds measured in bandpass noise to determine frequency resolution and off frequency hearing ability, (2a) gap detection in broadband noise to assess temporal acuity and threshold versus duration functions to determine temporal summation. Behavioral test of hearing will be assessed before and after carboplatin treatment and changes in hearing performance will be correlated with the degree of IHC loss. In addition, objective measures of OHC, distortion product otoacoustic emissions (DPOAE), will be obtained before and after carboplatin treatment. I hypothesize that basic function such as detection of tones in quiet will show little change after IHC damage. However, performance under background noise, gap detection, and temporal summation will be impaired in relation to the extent of IHC loss. I also hypothesize that these types of impairments could severely impact the ability to process complex sounds such as speech. PUBLIC HEALTH RELEVANCE: The consequences of selective IHC loss on hearing remain poorly understood despite their critical role as these cells synapse with over 90% of afferent auditory nerve fibers that transmit acoustic information to the brain. The overall goal of this project is to determine how auditory sensitivity, hearing in noise and temporal processing is altered when IHC and their afferent connections are damaged in chinchillas treated with the anticancer drug, carboplatin.